125301 20241125101151.0 doi 10.1039/d2bm01835g sideral 132941 ART-2023-132941 eng Bhandari, M. Subcellular localization and therapeutic efficacy of polymeric micellar nanoparticles encapsulating bedaquiline for tuberculosis treatment in zebrafish 2023 Access copy available to the general public Unrestricted The combination drug regimens that have long been used to treat tuberculosis (TB), caused by Mycobacterium tuberculosis, are fraught with problems such as frequent administration, long duration of treatment, and harsh adverse effects, leading to the emergence of multidrug resistance. Moreover, there is no effective preventive vaccine against TB infection. In this context, nanoparticles (NPs) have emerged as a potential alternative method for drug delivery. Encapsulating antibiotics in biodegradable NPs has been shown to provide effective therapy and reduced toxicity against M. tuberculosis in different mammalian models, when compared to conventional free drug administration. Here, we evaluate the localization, therapeutic efficacy and toxic effects of polymeric micellar NPs encapsulating a promising but highly hydrophobic and toxic antitubercular drug bedaquiline (BQ) in zebrafish embryos infected with Mycobacterium marinum. Our study shows that the NP formulation of BQ improves survival and reduces bacterial burden in the infected embryos after treatment when compared to its free form. The intravenously injected BQ NPs have short circulation times due to their rapid and efficient uptake into the endothelial cells, as observed by correlative light and electron microscopy (CLEM). info:eu-repo/grantAgreement/ES/DGA/E15-20R info:eu-repo/grantAgreement/ES/MEC/FPU2016-02456 info:eu-repo/grantAgreement/ES/MICINN/PID2019-109333RB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.8 2023 MATERIALS SCIENCE, BIOMATERIALS 12 / 53 = 0.226 2023 Q1 T1 1.206 2023 Materials Science (miscellaneous) 2023 Q1 Biomedical Engineering 2023 Q1 11.5 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Soria-Carrera, H. (orcid)0000-0002-5823-0314 Wohlmann, J. Knudsen Dal, N. J. Martínez de la Fuente, J. (orcid)0000-0003-1081-8482 Martín-Rapún, R. Universidad de Zaragoza (orcid)0000-0003-0702-8260 Griffiths, G. Fenaroli, F. 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica 11, 6 (2023), 2103-2114 Biomater. sci. Biomaterials Science 2047-4830 8238436 http://zaguan.unizar.es/record/125301/files/texto_completo.pdf Versión publicada 2740368 http://zaguan.unizar.es/record/125301/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:125301 articulos driver 2024-11-22-12:06:55 ARTICLE